Although the Wood-Ljungdahl pathway, a wide-spread pathway for CO2 fixation in anaerobic microorganisms, was elucidated in the thermophilic acetogenic bacterium Moorella thermoacetica, still relatively little is known about the enzymes involved in hydrogen oxidation, CO2 fixation, energy conservation and the role of quinones and cytochromes. Here, we have used transcriptomics, enzyme assays and genome analyses to identify missing links. NADPH, generated by a FeFe hydrogenase, is the reductant for CO2 reduction to formate, a key reaction in CO2 fixation. This reaction is slightly endergonic under standard conditions but becomes thermodynamically feasible at high environmental H2 concentrations. In addition, formate is taken out of equilibrium by a formate dehydrogenase that potentially forms a complex with an energy-converting hydrogenase (Fdh-Ech), a novel respiratory enzyme in acetogens. Under low H2 concentrations, the complex can drive the reverse, endergonic reaction. In addition, we postulate a formate cycle involving a periplasmic, cytochrome b-containing formate dehydrogenase. A NADH dehydrogenase-like enzyme that uses reduced ferredoxin instead of NADH to reduce menaquinone is also involved in energy conservation. The data are summarised in a comprehensive metabolic and bioenergetic model of acetogenesis from H2 + CO2 and CO in M. thermoacetica.
Rosenbaum et al. (Wed,) studied this question.